ESTABLISHMENT AND CHARACTERIZATION OF A NOVEL ACUTE PROMYELOCYTIC LEUKEMIA-CELL LINE (UF-1) WITH RETINOIC ACID-RESISTANT FEATURES

All-trans retinoic acid (RA) induces complete remission in a high prop ortion of patients with acute promyelocytic leukemia (APL). Neverthele ss, most of these patients develop RA resistance and relapse. The mech anisms of RA resistance by APL cells are still unclear. To understand the characteristics of human leukemia, human leukemic cell lines are u seful tools for study. APL cells have a strikingly low proliferation p otential in vitro; thus, only one APL cell line has been established. We developed a novel APL cell line (UF-1) from a patient clinically re sistant to all-trans RA. Cell surface markers in the UF-1 cells were p ositive for CD7, CD13, CD33, and CD38. Cytogenetic analyses revealed a dditional abnormalities, 46XX, add(1)(q44), add(6)(q12), add(7)(q36), t(15;17) (q21;q21). Molecular analyses showed a PML/RAR alpha fusion t ranscript, Sequence analysis of the RAR alpha gene in RA-resistant HL- 60 cells disclosed a point mutation in codon 411 (C to T substitution) , whereas UF-1 cells showed the normal sequence. All-trans RA did not change morphological features of the cell, NET reduction activity, or their expression of CD11b antigens as determined by FAGS analysis exce pt at 10(-6) mol/L. RA also did not alter the growth curve of the cell s as determined by the MTT assay. These findings suggest that the UF-1 cell is the first permanent cell line with spontaneous RA-resistant A PL cells. This RA-resistant APL cell line may be a useful model for mo lecular studies on the block of leukemic cell differentiation and as a means to investigate the mechanisms of RA resistance. (C) 1996 by The American Society of Hematology.